COVID-19Phase 2CCBCRISIS04NCT05166876
Brequinar Combined With Dipyridamole in Patients With Mild to Moderate COVID-19
A Phase 2 study testing Brequinar Sodium and Dipyridamole 75 MG in people with COVID-19, run by Clear Creek Bio, Inc. at 7 sites in India.
Trial summary
A Phase 2 multi-center, assessor-blind, randomized study to assess the safety, tolerability, and antiviral activity of brequinar in combination with dipyridamole. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- COVID-19
- What is being tested?
- Brequinar Sodium and Dipyridamole 75 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 7 sitesIndia
- Study dates
- 1 Feb 2022to 4 Jun 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Willing and able to provide informed consent for the trial, written, electronic, verbal, or other method deemed acceptable by the institution and IRB.
- Subjects between ≥18 and ≤65 years of age.
- Subjects found positive for SARS-CoV-2 either by rapid antigen test or by reverse transcription polymerase chain reaction (RT-PCR) using ICMR-validated kit.
- Note: Test need not be repeated in those with possession of confirmed positive report, but positive result test date must be ≤5 days of first dose of study drug.
- Mild or Moderate COVID-19 as per latest updated version of CLINICAL MANAGEMENT PROTOCOL for COVID-19 (in adults) released by Government of India Ministry of Health and Family Welfare Directorate General of Health Services (EMR Division).
- The effects of brequinar on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men and women treated or enrolled on this protocol must also agree to use adequate contraception for the duration of study participation, and for 90 days after completion of brequinar administration.
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- Male subjects must agree to refrain from sperm donation and female subjects must agree to refrain from ovum donation from initial study drug administration until 90 days after the last dose of brequinar.
- At least one non-respiratory COVID-19 symptom characterized as mild to moderate by the Investigator including but not limited to fatigue, chills, fever, body aches, nasal congestion, nausea, vomiting, or other sign or symptom commonly associated with COVID-19 in the opinion of the investigator. Symptom onset must be ≤5 days prior to first dose. Subject must have one or more signs/symptoms present at first dose.
- Willing to participate in the PK subset if at one of the identified sites.
- Able to swallow capsules.
Who cannot join
- 1. Have an oxygen saturation of <90% while breathing ambient air. 2. Any physical examination findings and/or history of any illness that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the subject.
- 3. Nursing women or women of childbearing potential (WOCBP) with a positive pregnancy test.
- 4. Treatment with another DHODH inhibitor (e.g., leflunomide, teriflunomide) or other agents known to cause bone marrow suppression leading to thrombocytopenia.
- 5. Ongoing treatment with aspirin and or dipyridamole, famotidine or cimetidine. Remdesivir and ivermectin are prohibited through Study Day 8. Steroids are permitted per the guidelines.
- 6. Platelets ≤125,000 cell/mm3. 7. Hemoglobin <10 gm/dL. 8. Absolute neutrophil count <1000 cells/mm3. 9. Renal dysfunction, i.e., creatinine clearance <30 mL/min. 10. AST or ALT >3 x ULN, or total bilirubin >ULN. Gilbert's Syndrome is allowed.
- 11. Bleeding disorders or blood loss requiring transfusion in the six weeks preceding enrollment.
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- 12. Ongoing gastrointestinal ulcer, or gastrointestinal bleeding within 6 weeks of first dose.
- 13. Chronic hepatitis B infection, active hepatitis C infection, active liver disease and/or cirrhosis per subject report.
- 14. Heart failure, current uncontrolled cardiovascular disease, including unstable angina, uncontrolled arrhythmias, major adverse cardiac event within 6 months (e.g., stroke, myocardial infarction, hospitalization due to heart failure, or revascularization procedure).
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
India7 sites
Rajarajeshwari Medical College and Hospital
Bangalore, Karnataka, 560060
Panimalar Hospital
Chennai, Tamil Nadu, 600123
Noble Hospital
Hadapsar, Pune, 411013
JIPMER Hospital
Puducherry, Puducherry, 605006
RIMS - Government Medical College
Srikakulam, Andhra Pradesh, 532001
Global Hospital
Surat, Gujarat, 395006
King George Hospital
Visakhapatnam, Andhra Pradesh, 531011
About this study
Official title: A Phase II, Randomized, Assessor-blind, Multicenter, Multi-dose, Placebo-controlled Study Assessing the Safety and Anti-coronavirus Response of Brequinar Combined With Dipyridamole in Patients With Mild to Moderate SARS-CoV-2 Infection.
A Phase 2 multi-center, assessor-blind, randomized study to assess the safety, tolerability, and antiviral activity of brequinar in combination with dipyridamole.
Read the detailed description
This is a Phase 2 clinical trial in two parts. The first part of the trial will study up to 64 subjects using a dose escalation approach, with 16 subjects per cohort for up to 4 cohorts. The brequinar dose will start at 50 mg per day in Cohort 1, escalating in the next cohort of 16 to 100 mg, then to 150 mg, and finally to 200 mg if safety parameters are met. The dipyridamole dose will be 75 mg three times a day (TID) for subjects assigned to the combination arm for all cohorts. All subjects will also receive standard of care (SOC) for treatment of patients with COVID-19 infection. After identifying the highest brequinar dose that is safe and well tolerated, 48 subjects will be treated in an expansion part comparing the chosen brequinar dose in combination with 75 mg dipyridamole TID to the chosen dose of brequinar alone. The combination of brequinar and dipyridamole shows potent in vitro antiviral activity by blocking DHODH and the pyrimidine salvage pathway, respectively, and the purpose of this study is to establish the safety and antiviral effect of the combination.
During the dose escalation part of the study, subjects with confirmed mild to moderate COVID-19 will receive 5 days of one of the following oral doses: brequinar alone, brequinar in combination with dipyridamole, or placebo. Subjects will have a Screening Visit followed as soon as possible with Study Day 1. Study visits (virtual or in person) will take place at Screening and on specified days. The visits that include bloodwork must be conducted at the study site or arrangements made for sample collection at the subject's home or other appropriate location. Other visits/visit activities for that visit may be conducted remotely using telemedicine or other remote technique. A viral load sample, vital signs (respiratory rate, heart rate, body temperature and SpO2), and a symptom assessment will be completed on specified days.
- Conditions
- COVID-19
- Being tested
- Brequinar Sodium, Dipyridamole 75 MG, Placebo
- Keywords
- SARS-CoV-2, Oral antiviral, DHODH Inhibitor, brequinar
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Brequinar SodiumDrug
50 mg, 100 mg, 150 mg, 200 mg x 5 days
Dipyridamole 75 MGDrug
75 mg TID for 5 days
PlaceboDrug
50 mg, 100 mg, 150 mg, 200 mg x 5 days
| Study group | Role | What they receive |
|---|---|---|
| Brequinar monotherapy | Experimental | Brequinar oral capsules will be administered once daily for 5 days using a dose-escalation approach. Planned doses include 50 mg, 100 mg, 150 mg, and 200 mg. Dosing will start at 50 mg and be escalated to the next higher dose if cohort stopping rules are not met. Receives: Drug: Brequinar Sodium |
| Placebo | Placebo comparator | Placebo matching brequinar oral capsules will be administered once daily for 5 days using a dose-escalation approach. Planned doses include 50 mg, 100 mg, 150 mg, and 200 mg. Dosing will start at 50 mg and be escalated to the next higher dose if cohort stopping rules are not met. Receives: Drug: Placebo |
| Brequinar-Dipyridamole Combination | Experimental | Brequinar oral capsules will be administered once daily for 5 days using a dose-escalation approach. Planned doses include 50 mg, 100 mg, 150 mg, and 200 mg. Dosing will start at 50 mg and be escalated to the next higher dose if cohort stopping rules are not met. All subjects assigned to this arm will also receive dipyridamole 75 mg tablets TID. Receives: Drug: Brequinar Sodium; Drug: Dipyridamole 75 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability of the Brequinar-dipyridamole Combination in COVID-19 Subjects
There were no subjects who experienced grade 3 and 4 toxicities and serious adverse events (SAEs) considered by the investigator to be related to the combination, brequinar alone or placebo alone. therefore frequencies of these events could not be compared.
Measured: Day 29
Secondary outcomes (5)
Reduction of SARS-CoV-2 Levels Using qPCR Through Day 29 and at Days 4, 8, 12, 15, 22, and 29
There were no subjects with detectable viral load after baseline, therefore no analyses could be conducted regarding change in viral load from baseline of SARS-CoV-2 levels using qPCR SARS-CoV-2 levels through Day 29 and at days 4, 8, 12, 15, 22, and 29
Measured: Day 29
Reduction in Time to Symptom Improvement
There were no subjects who had changes in symptom improvement, therefore no analyses of changes in symptom improvement could be conducted.
Measured: Day 29
Reduction in Percentage of Subjects Requiring Hospital Admission/Re-admission as an In-patient for >24 Hours
There were no subjects who required hospital admission/re-admission as an in-patient for >24 hours, therefore no analyses could be conducted for comparative change in percentage of subjects who required hospital admission/readmission for >24 hours.
Measured: Day 29
Reduction in Percentage of Subjects Requiring Medical Attended Visits, e.g., Hospitalization, Emergency Room Visits, Urgent Care/Family Doctor Visits
There were no subjects requiring medical attended visits, e.g., hospitalization, emergency room visits, Urgent Care/Family Doctor visits, therefore no analyses could be conducted for comparative change in percentage of subjects requiring medical attended visits, e.g., hospitalization, emergency room visits, Urgent Care/Family Doctor visits
Measured: Day 29
Reduction in Percentage of Subjects Requiring Supplemental Support Such as Oxygen
There were no subjects that required supplemental support such as oxygen, therefore analyses of comparative change in percentage of subjects requiring supplemental support such as oxygen could not be conducted.
Measured: Day 29
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Dec 2021
- Study start1 Feb 2022
- Primary completion4 Jun 2022
- Study completion4 Jun 2022
Why it stopped: Low prevalence of COVID-19 in India led to lack of eligible subjects.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for COVID-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- All subjects will receive standard of care. In addition, subjects will be randomly assigned to one of 3 treatments: brequinar (50 mg, 100 mg, 150 mg, or 200 mg), placebo (50 mg, 100 mg, 150 mg, or 200 mg), or brequinar + dipyridamole (75 mg TID) in a 2:1:1 ratio in Part 1 of the study using a dose escalation approach. An expansion cohort is planned with the highest safe brequinar dose.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Clear Creek Bio, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05166876
- Sponsor's protocol ID
- CCB-CRISIS-04
- Acronym
- CCBCRISIS04
- Status last verified
- Oct 2023
- First submitted
- 16 Dec 2021
- Last updated
- 7 Nov 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Randomized, Assessor-blind, Multicenter, Multi-dose, Placebo-controlled Study Assessing the Safety and Anti-coronavirus Response of Brequinar Combined With Dipyridamole in Patients With Mild to Moderate SARS-CoV-2 Infection.
- ClinicalTrials.gov ID
- NCT05166876
- Acronym / sponsor ID
- CCBCRISIS04 / CCB-CRISIS-04
- Conditions
- COVID-19
- Keywords
- SARS-CoV-2, Oral antiviral, DHODH Inhibitor, brequinar
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low prevalence of COVID-19 in India led to lack of eligible subjects.
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Clear Creek Bio, Inc.Industry (pharma, biotech, devices)
- Study start
- 1 Feb 2022 (actual)
- Primary completion
- 4 Jun 2022 (actual)
- Study completion
- 4 Jun 2022 (actual)
- First posted
- 22 Dec 2021 (actual)
- Results
- Posted 6 Feb 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A Phase 2 multi-center, assessor-blind, randomized study to assess the safety, tolerability, and antiviral activity of brequinar in combination with dipyridamole.
Detailed description
This is a Phase 2 clinical trial in two parts. The first part of the trial will study up to 64 subjects using a dose escalation approach, with 16 subjects per cohort for up to 4 cohorts. The brequinar dose will start at 50 mg per day in Cohort 1, escalating in the next cohort of 16 to 100 mg, then to 150 mg, and finally to 200 mg if safety parameters are met. The dipyridamole dose will be 75 mg three times a day (TID) for subjects assigned to the combination arm for all cohorts. All subjects will also receive standard of care (SOC) for treatment of patients with COVID-19 infection. After identifying the highest brequinar dose that is safe and well tolerated, 48 subjects will be treated in an expansion part comparing the chosen brequinar dose in combination with 75 mg dipyridamole TID to the chosen dose of brequinar alone. The combination of brequinar and dipyridamole shows potent in vitro antiviral activity by blocking DHODH and the pyrimidine salvage pathway, respectively, and the purpose of this study is to establish the safety and antiviral effect of the combination.
During the dose escalation part of the study, subjects with confirmed mild to moderate COVID-19 will receive 5 days of one of the following oral doses: brequinar alone, brequinar in combination with dipyridamole, or placebo. Subjects will have a Screening Visit followed as soon as possible with Study Day 1. Study visits (virtual or in person) will take place at Screening and on specified days. The visits that include bloodwork must be conducted at the study site or arrangements made for sample collection at the subject's home or other appropriate location. Other visits/visit activities for that visit may be conducted remotely using telemedicine or other remote technique. A viral load sample, vital signs (respiratory rate, heart rate, body temperature and SpO2), and a symptom assessment will be completed on specified days.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
- Model description
- All subjects will receive standard of care. In addition, subjects will be randomly assigned to one of 3 treatments: brequinar (50 mg, 100 mg, 150 mg, or 200 mg), placebo (50 mg, 100 mg, 150 mg, or 200 mg), or brequinar + dipyridamole (75 mg TID) in a 2:1:1 ratio in Part 1 of the study using a dose escalation approach. An expansion cohort is planned with the highest safe brequinar dose.
| Arm | Type | Receives |
|---|---|---|
| Brequinar monotherapy | Experimental | Drug: Brequinar SodiumBrequinar oral capsules will be administered once daily for 5 days using a dose-escalation approach. Planned doses include 50 mg, 100 mg, 150 mg, and 200 mg. Dosing will start at 50 mg and be escalated to the next higher dose if cohort stopping rules are not met. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo matching brequinar oral capsules will be administered once daily for 5 days using a dose-escalation approach. Planned doses include 50 mg, 100 mg, 150 mg, and 200 mg. Dosing will start at 50 mg and be escalated to the next higher dose if cohort stopping rules are not met. |
| Brequinar-Dipyridamole Combination | Experimental | Drug: Brequinar Sodium, Drug: Dipyridamole 75 MGBrequinar oral capsules will be administered once daily for 5 days using a dose-escalation approach. Planned doses include 50 mg, 100 mg, 150 mg, and 200 mg. Dosing will start at 50 mg and be escalated to the next higher dose if cohort stopping rules are not met. All subjects assigned to this arm will also receive dipyridamole 75 mg tablets TID. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Willing and able to provide informed consent for the trial, written, electronic, verbal, or other method deemed acceptable by the institution and IRB.
- Subjects between ≥18 and ≤65 years of age.
- Subjects found positive for SARS-CoV-2 either by rapid antigen test or by reverse transcription polymerase chain reaction (RT-PCR) using ICMR-validated kit.
- Note: Test need not be repeated in those with possession of confirmed positive report, but positive result test date must be ≤5 days of first dose of study drug.
- Mild or Moderate COVID-19 as per latest updated version of CLINICAL MANAGEMENT PROTOCOL for COVID-19 (in adults) released by Government of India Ministry of Health and Family Welfare Directorate General of Health Services (EMR Division).
Key exclusion criteria (9 listed)
- 1. Have an oxygen saturation of <90% while breathing ambient air. 2. Any physical examination findings and/or history of any illness that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the subject.
- 3. Nursing women or women of childbearing potential (WOCBP) with a positive pregnancy test.
- 4. Treatment with another DHODH inhibitor (e.g., leflunomide, teriflunomide) or other agents known to cause bone marrow suppression leading to thrombocytopenia.
- 5. Ongoing treatment with aspirin and or dipyridamole, famotidine or cimetidine. Remdesivir and ivermectin are prohibited through Study Day 8. Steroids are permitted per the guidelines.
- 6. Platelets ≤125,000 cell/mm3. 7. Hemoglobin <10 gm/dL. 8. Absolute neutrophil count <1000 cells/mm3. 9. Renal dysfunction, i.e., creatinine clearance <30 mL/min. 10. AST or ALT >3 x ULN, or total bilirubin >ULN. Gilbert's Syndrome is allowed.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Brequinar Sodium50 mg, 100 mg, 150 mg, 200 mg x 5 days | Drug | Brequinar monotherapy, Brequinar-Dipyridamole Combination |
| Dipyridamole 75 MG75 mg TID for 5 days | Drug | Brequinar-Dipyridamole Combination |
| Placebo50 mg, 100 mg, 150 mg, 200 mg x 5 days | Drug | Placebo |
Primary outcome
Safety and Tolerability of the Brequinar-dipyridamole Combination in COVID-19 Subjects
Time frame: Day 29
There were no subjects who experienced grade 3 and 4 toxicities and serious adverse events (SAEs) considered by the investigator to be related to the combination, brequinar alone or placebo alone. therefore frequencies of these events could not be compared.
5 secondary outcomes
Reduction of SARS-CoV-2 Levels Using qPCR Through Day 29 and at Days 4, 8, 12, 15, 22, and 29
Time frame: Day 29
Reduction in Time to Symptom Improvement
Time frame: Day 29
Reduction in Percentage of Subjects Requiring Hospital Admission/Re-admission as an In-patient for >24 Hours
Time frame: Day 29
Reduction in Percentage of Subjects Requiring Medical Attended Visits, e.g., Hospitalization, Emergency Room Visits, Urgent Care/Family Doctor Visits
Time frame: Day 29
Reduction in Percentage of Subjects Requiring Supplemental Support Such as Oxygen
Time frame: Day 29
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Brequinar Sodium and Dipyridamole 75 MG in people with COVID-19, run by Clear Creek Bio, Inc. at 7 sites in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 7 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and Tolerability of the Brequinar-dipyridamole Combination in COVID-19 Subjects (time frame: Day 29). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Nov 2023.